Development of a safe and effective AIDS vaccine has tremendous commercial potential and social impact and is a national priority. In response to the obstacles presented in AIDS vaccine development, a set of new concepts and designs is integrated to develop a new AIDS vaccine-adjuvant system. It includes a special design of immunogen HMP-gpl20, two novel adjuvants targeting B lymphocytes, and a new formulation of vaccine antigen-adjuvant. It could lead to a long-sought AIDS vaccine that elicits effective and long lasting neutralizing antibody responses to multiple HIV strains to prevent HIV infection and transmission. In the proposed Phase I study we will develop a new AIDS vaccine-adjuvant system, immunize animals, and detect general and neutralizing antibody activities that block HIV gpl20 binding to DC-SIGN. The investigators' experience, the preliminary data, the animal facility, and the company expertise make the scientific team competent to complete the objectives in this proposal. We anticipate that this novel AIDS vaccine-adjuvant system will induce strong neutralizing antibody activity and provide a model for elusive vaccines and a novel mechanism to enhance humoral immunity. The constructed HMP-gpl20, new adjuvants, and other reagents will be the basis for Phase II study. The neutralizing antibody activity will provide necessary information for phase II research and development.